Assessment of Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Invasion Into the Greater Curvature: A Randomized Clinical Trial.

Importance: The survival benefit of laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for locally advanced proximal gastric cancer (APGC) without invasion into the greater curvature remains uncertain. Objective: To compare the long-term and short-term efficacy of LSTG (D2 + No. 10 group) and conventional laparoscopic total gastrectomy (D2 group) for patients with APGC that has not invaded the greater curvature. Design, Setting, and Participants: In this open-label, prospective randomized clinical trial, a total of 536 patients with clinical stage cT2 to 4a/N0 to 3/M0 APGC without invasion into the greater curvature were enrolled from January 2015 to October 2018. The final follow-up was on October 31, 2021. Data were analyzed from December 2021 to February 2022. Interventions: Eligible patients were randomized to the D2 + No. 10 group or the D2 group. Main Outcomes and Measures: The primary outcome was 3-year disease-free survival (DFS). The secondary outcomes were 3-year overall survival (OS) and morbidity and mortality within 30 days after surgery. Results: Of 526 included patients, 392 (74.5%) were men, and the mean (SD) age was 60.6 (9.6) years. A total of 263 patients were included in the D2 + No. 10 group, and 263 were included in the D2 group. The 3-year DFS was 70.3% (95% CI, 64.8-75.8) for the D2 + No. 10 group and 64.3% (95% CI, 58.4-70.2; P = .11) for the D2 group, and the 3-year OS in the D2 + No. 10 group was better than that in the D2 group (75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2]; P = .02). Multivariate analysis revealed that splenic hilar lymphadenectomy was not an independent protective factor for DFS (hazard ratio [HR], 0.86; 95% CI, 0.63-1.16) or OS (HR, 0.81; 95% CI, 0.59-1.12). Stratification analysis showed that patients with advanced posterior gastric cancer in the D2 + No. 10 group had better 3-year DFS (92.9% vs 39.3%; P < .001) and OS (92.9% vs 42.9%; P < .001) than those in the D2 group. Multivariate analysis confirmed that patients with advanced posterior gastric cancer could have the survival benefit from No. 10 lymph node dissection (DFS: HR, 0.10; 95% CI, 0.02-0.46; OS: HR, 0.12; 95% CI, 0.03-0.52). Conclusions and Relevance: Although LSTG could not significantly improve the 3-year DFS of patients with APGC without invasion into the greater curvature, patients with APGC located posterior gastric wall may benefit from LSTG. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

Hospital volume, postoperative mortality, and costs after gastrectomy for gastric cancer in colombia: is there any association? / Volume hospitalar, mortalidade pós-operatória e custos após gastrectomia por câncer gástrico na colômbia: existe associação?

ABSTRACT BACKGROUND: There are no information in the literature associating the volume of gastrectomies with survival and costs for the health system in the treatment of patients with gastric cancer in Colombia. AIMS: The aim of this study was to analyze how gastrectomy for gastric cancer is associated with hospital volume, 30-day and 180-day postoperative mortality, and healthcare costs in Bogotá, Colombia. METHODS: A retrospective cohort study based on hospital data of all adult patients with gastric cancer who underwent gastrectomy between 2014 and 2016 using a paired propensity score. The surgical volume was identified as the average annual number of gastrectomies performed by the hospital. RESULTS: A total of 743 patients were included in the study. Hospital mortality at 30 and 180 days postoperatively was 36 (4.85%) and 127 (17.09%) patients, respectively. The average health care cost was USD 3,200. A total of 26 or more surgeries were determined to be the high surgical volume cutoff. Patients operated on in hospitals with a high surgical volume had lower 6-month mortality (HR 0.44; 95%CI 0.27-0.71; p=0.001), and no differences were found in health costs (mean difference 398.38; 95%CI-418.93-1,215.69; p=0.339). CONCLUSIONS: This study concluded that in Bogotá (Colombia), surgery in a high-volume hospital is associated with better 6-month survival and no additional costs to the health system.

RESUMO RACIONAL: Não há informações na literatura relacionando o volume de gastrectomias bem como a sobrevida e os custos para o sistema de saúde, no tratamento de pacientes com câncer gástrico na Colômbia. OBJETIVOS: analisar como a gastrectomia para câncer gástrico está associada ao volume hospitalar, mortalidade pós-operatória de 30 e 180 dias e custos de saúde em Bogotá, Colômbia. MÉTODOS: Estudo de coorte retrospectivo baseado em dados hospitalares de todos os pacientes adultos com câncer gástrico submetidos à gastrectomia entre 2014 e 2016, utilizando um escore de propensão pareado. O volume cirúrgico foi identificado como o número médio anual de gastrectomias realizadas pelo hospital. RESULTADOS: Foram incluídos no estudo 743 pacientes. A mortalidade hospitalar aos 30 e 180 dias de pós-operatório, foram respectivamente, 36 (4,85%) e 127 (17,09%) pacientes. O custo médio de saúde foi de US$ 3.200. Vinte e seis ou mais cirurgias foram determinadas como ponto de corte de alto volume cirúrgico. Pacientes operados em hospitais de alto volume cirúrgico tiveram menor mortalidade em seis meses (HR 0,44; IC95% 0,27-0,71; p=0,001) e não foram encontradas diferenças nos custos com saúde (diferença média 398,38; IC95% −418,93-1215,69; p=0,339). CONCLUSÕES: Este estudo concluiu que em Bogotá (Colômbia), a cirurgia em um hospital com alto volume cirúrgico está associada a uma melhor sobrevida de seis meses e não há custos adicionais para o sistema de saúde.

Prognostic Predictors After Surgical Intervention for Stage IV Gastric Cancer.

BACKGROUND/AIM: This study aimed to examine the efficacy of surgical intervention after chemotherapy for stage IV gastric cancer and the predictors of survival after surgical intervention. PATIENTS AND METHODS: Forty-three gastric cancer patients who had only one type of incurable factor (e.g., para-aortic lymph node metastasis) and had undergone initial chemotherapy, underwent chemotherapy alone (CX group; n=25), palliative gastrectomy (PS group; n=8), and conversion surgery (CS group; n=10). Their therapeutic outcomes were compared. RESULTS: The CS group had significantly higher 2-year overall survival rates (80%) than the CX group (25%), whose prognosis was similar to that of the PS group (23%; p<0.001). Pathological complete response of para-aortic lymph node or peritoneal metastases was an independent predictor of survival after surgery, as was >6 months of chemotherapy. CONCLUSION: CS may improve the prognosis of patients with stage IV gastric cancer in whom chemotherapy can achieve pathological disappearance of the metastatic lesions.

Clinical significance of controlling nutritional status score (CONUT) in evaluating outcome of postoperative patients with gastric cancer.

The stomach is the main digestive organ in humans. Patients with gastric cancer often develop digestive problems, which result in poor nutrition. Nutritional status is closely related to postoperative complications and quality of life (QoL) in patients with gastric cancer. The controlling nutritional status (CONUT) score is a novel tool to evaluate the nutritional status of patients. However, the relationship of the CONUT score with postoperative complications, QoL, and psychological status in patients with gastric cancer has not been investigated. The present follow-up study was conducted in 106 patients who underwent radical gastrectomy in our hospital between 2014 and 2019. The CONUT score, postoperative complications, psychological status, postoperative QoL scores, and overall survival (OS) of patients with gastric cancer were collected, and the relationship between them was analyzed. A significant correlation was observed between the CONUT score and postoperative complications of gastric cancer (P < 0.001), especially anastomotic leakage (P = 0.037). The multivariate regression analysis exhibited that the CONUT score (P = 0.002) is an independent risk factor for postoperative complications. The CONUT score was correlated with the state anxiety questionnaire (S-AI) for evaluating psychological status (P = 0.032). However, further regression analysis exhibited that the CONUT score was not an independent risk factor for psychological status. Additionally, the CONUT score was associated with postoperative QoL. The multivariate regression analysis exhibited that the CONUT score was an independent risk factor for the global QoL (P = 0.048). Moreover, the efficiency of CONUT score, prognostic nutrition index, and serum albumin in evaluating complications, psychological status, and QoL was compared, and CONUT score was found to outperform the other measures (Area Under Curve, AUC = 0.7368). Furthermore, patients with high CONUT scores exhibited shorter OS than patients with low CONUT scores (P = 0.005). Additionally, the postoperative complications (HR 0.43, 95% CI 0.21-0.92, P = 0.028), pathological stage (HR 2.26, 95% CI 1.26-4.06, P = 0.006), and global QoL (HR 15.24, 95% CI 3.22-72.06, P = 0.001) were associated with OS. The CONUT score can be used to assess the nutritional status of patients undergoing gastric cancer surgery and is associated with the incidence of postoperative complications and QoL.

Clinical impact of gastrectomy for gastric cancer patients with positive lavage cytology without gross peritoneal dissemination.

BACKGROUND: The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established. PATIENTS AND METHODS: In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care. RESULTS: One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p < 0.001). CONCLUSION: Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Surgical treatment of gastric adenocarcinoma: Are we achieving textbook oncologic outcomes for our patients?

BACKGROUND AND OBJECTIVES: Composite measures are increasingly used to assess quality of care in surgical oncology. We sought to define the incidence of "textbook oncologic outcome" (TOO) following resection of gastric adenocarcinoma among a large, international cohort of patients. METHODS: Gastric adenocarcinoma patients undergoing resection between 2000 and 2020 were identified from an international database. TOO was defined as margin-negative resection, examination of ≥16 lymph nodes, no prolonged length-of-stay (LOS), no 30-day mortality, and stage-appropriate receipt of chemotherapy. RESULTS: Among a total of 910 patients, 321 patients (35.3%) achieved a postoperative TOO. While failure to evaluate ≥16 lymph nodes (n = 591, 65.0%) and receipt of chemotherapy (n = 651, 71.5%) had the greatest negative impact on the ability to obtain a TOO, no 30-day mortality (n = 880, 96.7%), margin-negative resection (n = 831, 91.3%), and no extended LOS (n = 706, 77.6%) were more commonly achieved. No postoperative complications (OR: 0.44; 95% CI: 0.31-0.63) and T1a/T1b-stage disease (OR: 2.87; 95% CI: 1.59-5.18) were independently associated with achieving a TOO (p < 0.05). The odds of achieving a TOO improved over time (p-trend < 0.05), which was largely attributable to improved odds of evaluating ≥16 lymph nodes (2010-2014 vs. 2000-2004: OR, 5.21; 95% CI: 3.22-8.45). CONCLUSIONS: Only about one in three patients achieved a TOO following resection of gastric adenocarcinoma. Odds of TOO increased over time, largely due to improved lymph node evaluation.

The Clinical Significance of CA19-9 and Tumor Size Ratios for Predicting Prognosis After Conversion Surgery in Patients With Stage IV Gastric Cancer.

BACKGROUND/AIM: The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy. PATIENTS AND METHODS: We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS. RESULTS: The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients. CONCLUSION: Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS.

Comparative Safety of Sleeve Gastrectomy and Gastric Bypass Up to 5 Years After Surgery in Patients With Severe Obesity.

Importance: Sleeve gastrectomy is the most widely used bariatric operation; however, its long-term safety is largely unknown. Objective: To compare the risk of mortality, complications, reintervention, and health care use 5 years after sleeve gastrectomy and gastric bypass. Design, Setting, and Participants: This retrospective cohort study included adult patients in a national Medicare claims database who underwent sleeve gastrectomy or gastric bypass from January 1, 2012, to December 31, 2018. Instrumental variables survival analysis was used to estimate the cumulative incidence of outcomes up to 5 years after surgery. Exposures: Laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Main Outcomes and Measures: The main outcome was risk of mortality, complications, and reinterventions up to 5 years after surgery. Secondary outcomes were health care use after surgery, including hospitalization, emergency department (ED) use, and total spending. Results: Of 95 405 patients undergoing bariatric surgery, 57 003 (60%) underwent sleeve gastrectomy (mean [SD] age, 57.1 [11.8] years), of whom 42 299 (74.2%) were women; 124 (0.2%) were Asian; 10 101 (17.7%), Black; 1951 (3.4%), Hispanic; 314 (0.6%), North American Native; 43 194 (75.8%), White; 534 (0.9%), of other race or ethnicity; and 785 (1.4%), of unknown race or ethnicity. A total of 38 402 patients (40%) underwent gastric bypass (mean [SD] age, 55.9 [11.7] years), of whom 29 050 (75.7%) were women; 109 (0.3%), Asian; 6038 (15.7%), Black; 1215 (3.2%), Hispanic; 278 (0.7%), North American Native; 29 986 (78.1%), White; 373 (1.0%), of other race or ethnicity; and 404 (1.1%), of unknown race or ethnicity. Compared with patients undergoing gastric bypass, at 5 years after surgery, patients undergoing sleeve gastrectomy had a lower cumulative incidence of mortality (4.27%; 95% CI, 4.25%-4.30% vs 5.67%; 95% CI, 5.63%-5.69%), complications (22.10%; 95% CI, 22.06%-22.13% vs 29.03%; 95% CI, 28.99%-29.08%), and reintervention (25.23%; 95% CI, 25.19%-25.27% vs 33.57%; 95% CI, 33.52%-33.63%). Conversely, patients undergoing sleeve gastrectomy had a higher cumulative incidence of surgical revision at 5 years (2.91%; 95% CI, 2.90%-2.93% vs 1.46%; 95% CI, 1.45%-1.47%). The adjusted hazard ratio (aHR) of all-cause hospitalization and ED use was lower for patients undergoing sleeve gastrectomy at 1 year (hospitalization, aHR, 0.83; 95% CI, 0.80-0.86; ED use, aHR, 0.87; 95% CI, 0.84-0.90) and 3 years (hospitalization, aHR, 0.94; 95% CI, 0.90-0.98; ED use, aHR, 0.93; 95% CI, 0.90-0.97) after surgery but similar between groups at 5 years (hospitalization, aHR, 0.99; 95% CI, 0.94-1.04; ED use, aHR, 0.97; 95% CI, 0.92-1.01). Total health care spending among patients undergoing sleeve gastrectomy was lower at 1 year after surgery ($28 706; 95% CI, $27 866-$29 545 vs $30 663; 95% CI, $29 739-$31 587), but similar between groups at 3 ($57 411; 95% CI, $55 239-$59 584 vs $58 581; 95% CI, $56 551-$60 611) and 5 years ($86 584; 95% CI, $80 183-$92 984 vs $85 762; 95% CI, $82 600-$88 924). Conclusions and Relevance: In a large cohort of patients undergoing bariatric surgery, sleeve gastrectomy was associated with a lower long-term risk of mortality, complications, and reinterventions but a higher long-term risk of surgical revision. Understanding the comparative safety of these operations may better inform patients and surgeons in their decision-making.

Laparoscopic Versus Open Gastrectomy for Gastric Cancer (LOGICA): A Multicenter Randomized Clinical Trial.

BACKGROUND: The oncological efficacy and safety of laparoscopic gastrectomy are under debate for the Western population with predominantly advanced gastric cancer undergoing multimodality treatment. METHODS: In 10 experienced upper GI centers in the Netherlands, patients with resectable (cT1-4aN0-3bM0) gastric adenocarcinoma were randomly assigned to either laparoscopic or open gastrectomy. No masking was performed. The primary outcome was hospital stay. Analyses were performed by intention to treat. It was hypothesized that laparoscopic gastrectomy leads to shorter hospital stay, less postoperative complications, and equal oncological outcomes. RESULTS: Between 2015 and 2018, a total of 227 patients were randomly assigned to laparoscopic (n = 115) or open gastrectomy (n = 112). Preoperative chemotherapy was administered to 77 patients (67%) in the laparoscopic group and 87 patients (78%) in the open group. Median hospital stay was 7 days (interquartile range, 5-9) in both groups (P = .34). Median blood loss was less in the laparoscopic group (150 v 300 mL, P < .001), whereas mean operating time was longer (216 v 182 minutes, P < .001). Both groups did not differ regarding postoperative complications (44% v 42%, P = .91), in-hospital mortality (4% v 7%, P = .40), 30-day readmission rate (9.6% v 9.1%, P = 1.00), R0 resection rate (95% v 95%, P = 1.00), median lymph node yield (29 v 29 nodes, P = .49), 1-year overall survival (76% v 78%, P = .74), and global health-related quality of life up to 1 year postoperatively (mean differences between + 1.5 and + 3.6 on a 1-100 scale; 95% CIs include zero). CONCLUSION: Laparoscopic gastrectomy did not lead to a shorter hospital stay in this Western multicenter randomized trial of patients with predominantly advanced gastric cancer. Postoperative complications and oncological efficacy did not differ between laparoscopic gastrectomy and open gastrectomy.

Florid Foreign Body-type Giant Cell Response to Keratin Is Associated With Improved Overall Survival in Patients Receiving Preoperative Therapy for Esophageal Squamous Cell Carcinoma.

While most resection specimens from patients with neoadjuvantly treated esophageal squamous cell carcinoma show therapy-related changes in the form of inflammation and fibrosis, others harbor a florid foreign body-type giant cell response to keratin debris. The purpose of our study was to perform a detailed clinicopathologic analysis of these histologic types of treatment responses and correlate these findings with patient outcome. Clinical and pathologic parameters from 110 esophagogastrectomies were recorded and analyzed. Two main types of histologic responses were observed: inflammatory-predominant response (59%) and florid foreign body-type giant cell response to keratin (41%). Irrespective of cG, cTNM, and amount of residual cancer, florid foreign body-type giant cell reaction was predominantly noted deep within the esophageal wall, while the inflammatory response was restricted to the mucosa, submucosa, and inner half of muscularis propria. Patients with foreign body-type giant cell response showed significantly better overall survival compared with the inflammatory response group (log-rank test P=0.015). Florid foreign body-type giant cell response was the only factor associated with improved survival in a multivariable analysis for overall survival (hazard ratio=0.5; 95% confidence interval=0.3-1.0; P=0.038), but not in the model for disease-specific survival, whereas ypTNM stage II was the only significant risk factor for disease-specific survival in multivariable analysis (hazard ratio=3.4; 95% confidence interval=1.0-11.2; P=0.047). Our results suggest that in addition to the College of American Pathologists Tumor Regression Score and ypTNM stage, subtype of histologic response to therapy may represent another prognostic marker for neoadjuvantly treated esophageal squamous cell carcinoma.

Effect of Bariatric Surgery on Survival and Hospitalizations in Patients with Severe Obesity. A Retrospective Cohort Study.

Bariatric surgery (BS) confers a survival benefit in specific subsets of patients with severe obesity; otherwise, effects on hospital admissions are still uncertain. We assessed the long-term effect on mortality and on hospitalization of BS in patients with severe obesity. This was a retrospective cohort study, including all patients residing in Piedmont (age 18-60 years, BMI ≥ 40 kg/m2) admitted during 2002-2018 to the Istituto Auxologico Italiano. Adjusted hazard ratios (HR) for BS were estimated for mortality and hospitalization, considering surgery as a time-varying variable. Out of 2285 patients, 331 (14.5%) underwent BS; 64.4% received sleeve gastrectomy (SG), 18.7% Roux-en-Y gastric bypass (RYGB), and 16.9% adjustable gastric banding (AGB). After 10-year follow-up, 10 (3%) and 233 (12%) patients from BS and non-BS groups died, respectively (HR = 0.52; 95% CI 0.27-0.98, by a multivariable Cox proportional-hazards regression model). In patients undergoing SG or RYGB, the hospitalization probability decreased significantly in the after-BS group (HR = 0.77; 0.68-0.88 and HR = 0.78; 0.63-0.98, respectively) compared to non-BS group. When comparing hospitalization risk in the BS group only, a marked reduction after surgery was found for all BS types. In conclusion, BS significantly reduced the risk of all-cause mortality and hospitalization after 10-year follow-up.

Adjuvant chemotherapy is an additional option for locally advanced gastric cancer after radical gastrectomy with D2 lymphadenectomy: a retrospective control study.

BACKGROUND: This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. METHODS: We retrospectively identified 428 patients with stage II-III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7-8 cycles every 3 weeks or 10-12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4-6 cycles every 3 weeks or 6-9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4-6/6-9 and 7-8/10-12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). CONCLUSIONS: To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4-6 cycles every 3 weeks or FOLFOX regimen for 6-9 cycles every 2 weeks might be a favorable option for patients with stage II-III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.

Impact of neoadjuvant therapy followed by laparoscopic radical gastrectomy with D2 lymph node dissection in Western population: A multi-institutional propensity score-matched study.

BACKGROUND AND OBJECTIVES: In the setting of a minimally invasive approach, we aimed to compare short and long-term postoperative outcomes of patients treated with neoadjuvant therapy (NAT) + surgery or upfront surgery in Western population. METHODS: All consecutive patients from six Italian and one Serbian center with locally advanced gastric cancer who had undergone laparoscopic gastrectomy with D2 lymph node dissection were selected between 2005 and 2019. After propensity score-matching, postoperative morbidity and oncologic outcomes were investigated. RESULTS: After matching, 97 patients were allocated in each cohort with a mean age of 69.4 and 70.5 years. The two groups showed no difference in operative details except for a higher conversion rate in the NAT group (p = 0.038). The overall postoperative complications rate significantly differed between NAT + surgery (38.1%) and US (21.6%) group (p = 0.019). NAT was found to be related to a higher risk of postoperative morbidity in patients older than 60 years old (p = 0.013) but not in patients younger (p = 0.620). Conversely, no difference in overall survival (p = 0.41) and disease-free-survival (p = 0.34) was found between groups. CONCLUSIONS: NAT appears to be related to a higher postoperative complication rate and equivalent oncological outcomes when compared with surgery alone. However, poor short-term outcomes are more evident in patients over 60 years old receiving NAT.

Body composition parameters predict pathological response and outcomes in locally advanced gastric cancer after neoadjuvant treatment: A multicenter, international study.

BACKGROUND: Body composition profiles influence the prognosis of several types of cancer; however, the role of body composition in patients with locally advanced gastric cancer (LAGC) after neoadjuvant treatment (NT) has not been well characterized. PATIENTS AND METHODS: A total of 213 patients with LAGC who underwent gastrectomy after NT at a high-volume institution from southern China were comprehensively evaluated for primary analysis. Additionally, 170 and 77 patients from Western China and Italy, respectively, were reviewed for external validation. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and the subcutaneous as well as the visceral adiposity index were assessed from clinically acquired CT scans at diagnosis and preoperatively. RESULTS: Overall, none of the body composition parameters significantly changed after NT. The pre-NT skeletal muscle radiodensity (SMD) and change in SMI (ΔSMI) were both significantly lower in the patients with poor response (tumor regression <50%; mean SMD: 43.5 vs 46.5, P = 0.003; mean ΔSMI: -1.0 vs 2.2, P < 0.001), and the cutoff values were calculated according to the Youden index as 43.7 and 1.2, respectively. Based on these 2 parameters, a novel model, the Skeletal Muscle Score (SMS), was proposed to predict the pathological response (AUC = 0.764 alone and = 0.822 in combination with the radiological response). Moreover, patients with an SMI loss >1.2 had a significantly prolonged drainage tube removal time (mean: 10.0 vs 8.2, P = 0.003) and postoperative hospital stay (mean: 11.1 vs 9.8, P = 0.048), as well as a significantly higher rate of postoperative complications (30.9% vs 16.7%, P = 0.015). In the multivariate analysis, SMI loss >1.2 independently predicted poor overall survival (HR: 1.677, 95% CI 1.040-2.704, P = 0.034) and recurrence-free survival (HR: 1.924, 95% CI 1.165-3.175, P = 0.011). ΔSMI was also significantly associated with pathological response, surgical outcomes, and survival in the 2 external cohorts (P all < 0.05). CONCLUSIONS: For LAGC, the pre-NT SMD and ΔSMI could accurately predict the pathological response after NT. An SMI loss >1.2 is closely associated with poorer outcomes and may indicate the need more supportive treatment.

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Assessment of copy number in protooncogenes are predictive of poor survival in advanced gastric cancer.

The copy number (CN) gain of protooncogenes is a frequent finding in gastric carcinoma (GC), but its prognostic implication remains elusive. The study aimed to characterize the clinicopathological features, including prognosis, of GCs with copy number gains in multiple protooncogenes. Three hundred thirty-three patients with advanced GC were analyzed for their gene ratios in EGFR, GATA6, IGF2, and SETDB1 using droplet dPCR (ddPCR) for an accurate assessment of CN changes in target genes. The number of GC patients with 3 or more genes with CN gain was 16 (4.8%). Compared with the GCs with 2 or less genes with CN gain, the GCs with 3 or more CN gains displayed more frequent venous invasion, a lower density of tumor-infiltrating lymphocytes, and lower methylation levels of L1 or SAT-alpha. Microsatellite instability-high tumors or Epstein-Barr virus-positive tumors were not found in the GCs with 3 or more genes with CN gain. Patients of this groups also showed the worst clinical outcomes for both overall survival and recurrence-free survival, which was persistent in the multivariate survival analyses. Our findings suggest that the ddPCR-based detection of multiple CN gain of protooncogenes might help to identify a subset of patients with poor prognosis.

Prognostic impact of dimensional factors in pT1 gastric cancer.

BACKGROUND: The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer. OBJECTIVES: This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer. METHODS: We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve. RESULTS: Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. CONCLUSIONS: The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

Ninety-day mortality after total gastrectomy for gastric cancer.

BACKGROUND: Total gastrectomy for gastric cancer is associated with significant 30-day mortality, but this endpoint may underestimate the short-term mortality of the procedure. METHODS: Retrospective analysis was performed using the National Cancer Database (2004-2015). Patients who underwent total gastrectomy for stage I to III gastric adenocarcinoma were identified and divided into cohorts based on 90-day mortality. Predictors of mortality were analyzed using multivariable logistic regression, and annual trends in mortality rates were calculated by Joinpoint Regression. RESULTS: Of the 5,484 patients who underwent total gastrectomy, 90-day and 30-day mortality rates were 9.1% and 4.7%, respectively. Factors associated with 90-day mortality included increasing age (odds ratio 1.0, P < .001), income below the median (odds ratio 1.2, P = .039), Charlson-Deyo score ≥2 (odds ratio 1.4, P = .039), treatment at low-volume facilities (odds ratio 1.5, P < .001), N1 (odds ratio 2.0, P < .001), N2 (odds ratio 2.0, P < .001), or N3 (odds ratio 2.7, P < .001) stage disease, having <16 lymph nodes harvested (odds ratio 1.5, P < .001), and lack of treatment with chemotherapy (3.7, P < .001). Lack of health insurance (odds ratio 4.1, P = .080), and positive microscopic margins (odds ratio 1.3, P = .080) were correlated, but not significantly associated, with 90-day mortality. The 90-day mortality rate significantly declined from 14.3% in 2004 to 7.9% in 2015 (P = .006), and the 30-day mortality rate significantly declined from 7.7% in 2004 to 4.8% in 2015 (P = .009). CONCLUSION: Nearly half of the deaths within 90 days after total gastrectomy for cancer occur beyond 30 days postoperative. Ninety-day mortality has improved over time, but rates remain high, suggesting the need for improved out-of-hospital postoperative care beyond 30 days.

High CD8/CD33 ratio in peritoneal metastatic lesions is associated with favorable prognosis in gastric cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and other immune cells have been reported as a prognostic factor in several tumors, including gastric cancer, and they play an important role in antitumor effect at the primary site. There were few reports on the immune status in peritoneal metastatic lesions for gastric cancer. AIMS: The aims of this study were to assess the prognostic significance of TILs (CD4, CD8, CD19, regulatory T cells [Tregs]), and myeloid-derived suppressor cells (MDSCs) in peritoneal metastatic lesions. METHODS: We retrospectively investigated 60 patients for gastric cancer with peritoneal metastasis who were treated between 2009 and 2016 in our institute. Immunohistochemistry for CD4, CD8, CD19, FOXP3, and CD33 was performed in the peritoneal metastatic lesions. The absolute numbers of immune cells and ratios were evaluated, and the relationship between immune-related marker and overall survival (OS) was investigated. RESULTS: A high infiltration of CD8+ lymphocytes or high CD8/CD33 ratio was a better prognosis for OS in univariate analysis using all immunologic variables (P = .012, P = .001). In multivariate analysis for clinical and immunologic variables, high CD8/CD33 ratio was identified as an independent prognostic factor for OS (Hazard ratio: 0.291, 95% confidence interval: 0.126-0.670, P = .004). CONCLUSION: High CD8/CD33 ratio and high infiltration of CD8+ lymphocytes in peritoneal metastatic lesions were favorable prognoses for gastric cancer patients with peritoneal metastasis. It is necessary to modify the immune microenvironment result to increase the level of CD8+ lymphocytes in the peritoneal metastatic lesions.

Impact of chronic kidney disease on the short- and long-term outcomes of laparoscopic gastrectomy for gastric cancer patients.

BACKGROUNDS: This study was undertaken to investigate the impact of coexisting chronic kidney disease (CKD) on short- and long-term outcomes of laparoscopic gastrectomy in patients with gastric cancer (GC). METHODS: We reviewed the data of 798 patients treated for GC by laparoscopic gastrectomy. All procedures took place between January 2010 and December 2017. Patients were divided into three groups according to their estimated glomerular filtration rate (eGFR): severe CKD group, 44 patients with eGFR < 45 mL/min/1.73 m2; moderate CKD group, 117 patients with 45 ≤ eGFR < 60; control group, 637 patients with eGFR ≥ 60. RESULTS: Based on multivariate analysis, severe CKD (eGFR < 45) emerged as an independent predictor of anastomotic leak (Hazard ratio 4.63, 95% confidence interval [CI] 1.62-11.54). The 5-year overall survival (OS) rates by group were 46.3% (severe CKD), 76.6% (moderate CKD), and 81.5% (control). Multivariate analysis likewise identified severe CKD (eGFR < 45) as an independent correlate of poor 5-year OS. The 5-year cancer-specific survival (CSS) rates did not differ significantly by group. CONCLUSIONS: An eGFR value less than 45 mL/min/1.73 m2 is a useful factor for predicting both anastomotic leak and 5-year OS in GC patients undergoing laparoscopic gastrectomy. Clinical care to improve eGFR should be reinforced before and after gastrectomy for GC patients with severe CKD.